Phase I Study of Flavopiridol in Combination With Cisplatin in Patients With Advanced Malignancies
alvocidib
+ carboplatin
+ cisplatin
Urogenital Diseases+19
+ Genital Diseases
+ Breast Diseases
Treatment Study
Summary
Study start date: December 1, 1998
Actual date on which the first participant was enrolled.OBJECTIVES: Determine the maximum tolerated dose (MTD) of flavopiridol and cisplatin in patients with advanced solid tumors. (Part 1) Determine the MTD of carboplatin when combined with flavopiridol in another group of patients with advanced solid tumors. (Part 2) Determine the toxic effects of these regimens in this patient population. Determine the objective clinical response in patients treated with this regimen. Determine the pharmacokinetics of these regimens in this patient population. OUTLINE: This is a dose-escalation study of flavopiridol and cisplatin (part 1), followed by a dose-escalation study of carboplatin (part 2). Part 1: Patients receive flavopiridol IV over 24 hours. Two weeks later, patients receive cisplatin IV over 2 hours immediately followed by flavopiridol IV over 24 hours. Treatment with cisplatin/flavopiridol continues every 3 weeks in the absence of unacceptable toxicity or disease progression. Sequential dose escalation of flavopiridol is followed by sequential dose escalation of cisplatin. Cohorts of 3-6 patients receive escalating doses of flavopiridol and then cisplatin until the maximum tolerated dose (MTD) of the combination is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity. Part 2: Additional patients are accrued for part 2. Those patients receive carboplatin IV over 30 minutes immediately followed by flavopiridol IV over 24 hours. Treatment continues every 3 weeks in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of carboplatin until the MTD is determined. The MTD is defined as in part 1. PROJECTED ACCRUAL: Approximately 36-48 patients will be accrued for this study within 2 years.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.48 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 18 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
DISEASE CHARACTERISTICS: Histologically confirmed unresectable advanced solid tumor for which no standard therapy exists that is potentially curative or definitely capable of extending life expectancy Biopsy confirmation of recurrent tumors required, unless sole site of disease is inaccessible bony and/or pulmonary metastases Eligible solid tumors include, but not are limited to, prostate cancer, breast cancer, or melanoma No lymphoma No CNS metastases Patients with primary brain tumors are eligible if they are not receiving antiepileptic medication(s) but are receiving stable doses of corticosteroids Hormone receptor status: Not specified PATIENT CHARACTERISTICS: Age: 18 and over Sex: Not specified Menopausal status: Not specified Performance status: ECOG 0-2 Life expectancy: See Disease Characteristics At least 12 weeks Hematopoietic: WBC at least 3,500/mm^3 Absolute neutrophil count at least 1,700/mm^3 Platelet count at least 100,000/mm^3 Hemoglobin at least 8 g/dL Hepatic: Bilirubin within upper limit of normal (ULN) AST and ALT no greater than 2.5 times ULN Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine no greater than 1.5 times ULN Cardiovascular: No New York Heart Association class III or IV heart disease No history of angina Neurologic: No grade 2 or greater peripheral neuropathy No seizure disorder Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No uncontrolled infection PRIOR CONCURRENT THERAPY: Biologic therapy: More than 4 weeks since prior immunotherapy More than 4 weeks since prior biologic therapy No concurrent immunotherapy Chemotherapy: More than 4 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) and recovered No other concurrent chemotherapy Endocrine therapy: See Disease Characteristics Radiotherapy: More than 4 weeks since prior radiotherapy No prior radiotherapy to more than 25% of bone marrow No concurrent radiotherapy Surgery: See Disease Characteristics
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location